Parkinson's disease (PD) is a disease of the central nervous system characterized by the reduction of dopamine (DA)-producing nerve cells in the substantia nigra, which results in chronic and progressive motor impairment. As late stage PD patients become intolerant of or resistant to the standard pharmacological therapies, surgical grafting of fetal ventral mesencephalic tissues in brains of PD patients have met with good success. However, the use of human fetal cells remains problematic due to the limited availability of tissue and the associated ethical, legal and social concerns. Xenotransplantations brings a potential risk for zoonotic and xenogeneic infections and potential serious side effects from a lifetime immunosuppressant regimen post-surgery. Spheramine(TM) is a novel, implantable cell based potential therapy for PD, consisting of cultured DA- producing human retinal pigmented epithelial (hRPE) cells on gelatin microcarriers which enhance their survival in vivo. Toxicology studies in nonhuman primates have demonstrated the safety of Spheramine. A pivotal preclinical study has established the efficacious dose range for Spheramine implantation in the MPTP hemiparkinsonian monkey without need for immunosuppression. The primary objective of this study is to test the safety and efficacy of intrastriatal implantation of Spheramine in Hoehn and Yahr stage III and IV Parkinson's patients. PROPOSED COMMERCIAL APPLICATIONS: There are approximately 2 million Parkinson's patients worldwide. At the later stages of the disease there is a decreased response to medication. Spheramine(TM) is a human cell-based therapy being developed for the treatment of Parkinson's Disease (PD). It is believed that the stereotaxic implantation of Spheramine in the striata of Parkinson's patients will be efficacious and more consistent in restoring function than current transplant procedures, and that concurrent immunosuppression will not be required. The proposed research will facilitate the development of this novel therapy for PD.